There are over 13 million medical articles and devices utilized annually in the United States for prophylactic and/or therapeutic treatment. These items range in sophistication from simple devices such as hernia repair mesh, wound dressings and catheter cuffs—to more complex implantable devices such as the total implantable heart, left ventricular assist devices and prosthetic arterial grafts. Although utilization of these medical articles and devices has improved the health and quality of life for the patient population as a whole, the in-vivo application of all such medical implements are prone to two major kinds of complications: infection and incomplete/non-specific cellular healing.
In general, regardless of the particular causative agent, infection remains one of the major complications associated with utilizing biomaterials, with the clinical infection occurring at either acute or delayed time periods after in-vivo use or implantation of the medical article or device. Today, surgical site infections account for approximately 14-16% of the 2.4-million nosocomial infections in the United States, and result in an increased patient morbidity and mortality. The inherent bulk properties of various biomaterials that comprise these articles and devices typically provide a milieu for initial bacterial/fungus adhesion with subsequent biofilm production and growth.
Similarly, unregulated cellular growth affects various medical devices such as stents and vascular grafts. Occlusion rates for diseased blood vessels after placement of a bare metallic stent (restenosis) have been reported as high as 27%, a significant problem based on the 1.1 million stents annually implanted. Moreover, since the currently available biomaterials in these medical articles and devices are typically comprised of foreign polymeric compounds, these biomaterials do not emulate the multitude of dynamic biologic and healing processes that occur in normal tissue; and consequently, the cellular components normally present within native living tissue are not available for controlling and/or regulating the reparative process. Thus, the search continues today for novel biomaterials (such as drug releasing biomaterials) that would direct or enhance some of the normal healing processes of native tissue, and would decrease patient morbidity and mortality rates.
Currently, drug delivery from a majority of implantable medical devices such as stents is achieved via the coating/sealing of a device or scaffold with a biodegradable polymer composition which serves as a drug reservoir. There are several potential problems with utilizing this system in that: (1) polymer coating onto the device can be inconsistent, resulting in areas with minimum/no localized drug release; (2) polymer coating efficiency can be limited based on the device design or composition of the base material; (3) drug release is dependent on biodegradation of the polymer reservoir, resulting in inconsistent drug release; and (4) application of the exogenous polymer can have adverse effects on tissue/organ healing or upon the biocompatibility (i.e. increasing thrombogenecity) of the original implant.
Electrospinning provides a technique for making nanofibrous material substrates. Electrospinning to produce nanoscale fibers, fabrications and textiles, however, is still a manufacturing technique in need of further development and refinement. Utilization of electrospinning as a technique to synthesize various nanofibrous materials from polymers such as polyurethane, polyvinyl alcohol (or “PVA”), poly(lactic glycolic) acid (or “PLGA”), nylon, and polyethylene oxide has been investigated for several decades (see for example Subbiah et al., “Electrospinning Of Nanofibers”, J. Applied Polymer Sci. 96:557-569 (2005).
While inclusion of bioactive agents has been accomplished for several other polymers (such as polyurethane, PLGA, alginate and collagen), the electrospinning technique has not been realized for polyethylene terephthalate (“PET”), or “polyester” as understood generally in textile circles, until recently. Since then, Ma et al. was able to electrospin polyethylene terephthalate using a melt-spinning technology [see Ma Z, Kotaki M, Yong T, He W, Ramakrishna S., “Surface engineering of electrospun polyethylene terephthalate (PET) nanofibers towards development of a new material for blood vessel engineering”, Biomaterials 26:2527 (2005)]. However, the Ma et al. reported technique requires a surface modification in which formaldehyde and several cross-linkers were utilized post-spinning subsequently to incorporate gelatin, owing to the high temperatures employed in their manufacturing process. These modification procedures are and remain a major issue because of their high temperature requirements and the consequential failure of the protein (or other temperature sensitive agent) to maintain its characteristic biological activity throughout the material fabrication process.
Accordingly, despite all these developments to date, there remains a recognized and continuing need for further improvements in the making of medical devices and articles comprised of nanofibrous materials which would demonstrate adequate physical strength characteristics and durability as fabricated items, and which would serve as biomedical constructs formed of fibrous materials having demonstrable biologically active properties. All such improvements in the making and/or preparation of such nanofibrous materials and articles would be readily seen as a major advantage and outstanding benefit in the medical field.